Frequency and Seasonal Variations of Viruses Causing Respiratory Tract Infections in Children Pre- and Post-COVID-19 Pandemic in Riyadh (2017–2022)

Introduction The COVID-19 pandemic has had a major impact on healthcare systems throughout the world. As the clinical and epidemiological features of COVID-19 share many similarities with other respiratory viruses in children, ensuring optimal management of different viral respiratory diseases is critical. The precautions taken to prevent COVID-19 have seemingly had an indirect effect on the seasonal variations of viral diseases and the frequency of relevant viruses. The seasonal irregularity of and uncertainty surrounding these infection peaks may affect the clinical prediction and management resources. Therefore, the aim of this study is to evaluate the impact of the COVID-19 pandemic on the frequency and seasonal variation of common respiratory viruses in children pre- and post-pandemic. Methodology This study utilizes a descriptive cross-sectional retrospective approach. A total of 726 samples collected from children below 14 years of age and admitted to King Abdulla bin Abdulaziz University Hospital between March 2017 and February 2022 were included in the present study to evaluate the impact of the COVID-19 pandemic on the frequency and seasonal variation of common respiratory viruses in children pre- and post-pandemic. The samples taken before March 15, 2020, were considered pre-COVID-19, and those taken from March 15, 2020, onward were considered post-COVID-19. The seasons were divided based on the months of the year as per the Saudi climate website (winter: December-February, spring: March-April, summer: May-August, and autumn: September-November). Results All nasopharyngeal swabs (NPS) for viral Polymerase chain reaction (PCR) multiplex that were done for all admitted children of age up to 14 years were included, and the total samples amounted to 726, There were 686 (94.4%) positive samples for viruses and 40 (5.5%) negative samples. The number of positive samples pre-COVID-19 pandemic was 494 (72%), and the number of positive samples post-COVID-19 pandemic was 192 (28%). The frequency of different viruses has decreased post-COVID-19 and seasonality has changed; Although Adenovirus, and influenza viruses have no big changes, but Human Rhino/enterovirus (HRE) has increased frequency post-COVID-19 (49%), while post-COVID-19 it was (29.1%). The seasonal peak for Respiratory Syncytial Virus (RSV) pre-COVID-19 showed mainly in winter (49%), while post-COVID-19 it showed no peak. Conclusion The frequency of most types of viruses is noted to be lesser in the post-COVID-19 period, most likely due to precautions followed during the pandemic. This is not the case for HRE which showed increasing frequency in post-COVID-19; However, there are clinically and statistically significant differences among seasonal peaks in Respiratory RSV, HRE, and Parainfluenza viruses (PIV) pre- and post-COVID-19 pandemic. RSV showed no peak in different seasons post-COVID-19, although its peak pre-COVID-19 was in winter and autumn; Additionally typical trend of HRE peak changed to be in Autumn and spring post-COVID-19 instead of winter pre-COVID-19.


Results
All nasopharyngeal swabs (NPS) for viral Polymerase chain reaction (PCR) multiplex that were done for all admitted children of age up to 14 years were included, and the total samples amounted to 726, There were 686 (94.4%) positive samples for viruses and 40 (5.5%) negative samples. The number of positive samples pre-COVID-19 pandemic was 494 (72%), and the number of positive samples post-COVID-19 pandemic was 192 (28%). The frequency of different viruses has decreased post-COVID-19 and seasonality has changed; Although Adenovirus, and influenza viruses have no big changes, but Human Rhino/enterovirus (HRE) has increased frequency post-COVID-19 (49%), while post-COVID-19 it was (29.1%). The seasonal peak for Respiratory Syncytial Virus (RSV) pre-COVID-19 showed mainly in winter (49%), while post-COVID-19 it showed no peak.

Conclusion
The frequency of most types of viruses is noted to be lesser in the post-COVID-19 period, most likely due to precautions followed during the pandemic. This is not the case for HRE which showed increasing frequency in post-COVID-19; However, there are clinically and statistically significant differences among seasonal peaks in Respiratory RSV, HRE, and Parainfluenza viruses (PIV) pre-and post-COVID-19 pandemic. RSV showed no peak in different seasons post-COVID-19, although its peak pre-COVID-19 was in winter and autumn; Additionally typical trend of HRE peak changed to be in Autumn and spring post-COVID-19 instead of winter pre-COVID-19.

Introduction
The COVID-19 pandemic has had a major impact on healthcare systems throughout the world. As the clinical and epidemiological features of COVID-19 share many similarities with other respiratory viruses in children, ensuring optimal management of different viral respiratory diseases is crucial. The precautions followed to prevent COVID-19 (including travel restrictions and closure of workplaces and schools, as well as social distancing, mask usage, and hand hygiene) have an indirect effect on the seasonal variation of viral diseases and the frequency of relevant viruses.
Some studies showed that both in Europe and Australia, only a few RSV cases have been detected even after the removal of the most restrictive measures, i.e., when only hand washing, social distancing, and mandatory face mask usage were maintained [1,2].
Despite the above-mentioned precautions, rhinovirus cases were noted to increase in frequency during the COVID-19 pandemic while the frequency of infections caused by enveloped viruses (influenza A; human metapneumovirus; human parainfluenza virus types 1, 2, 3, and 4; and human respiratory syncytial virus) decreased.
The seasonal irregularity of and uncertainty regarding these infection peaks may affect the clinical prediction and management resources. This research could help in developing a prospective therapeutic approach for viral respiratory tract infections in children.
The objective of this research was to describe the seasonal variation of common respiratory viruses in children pre-and post-COVID-19-pandemic and identify the frequency of each virus causing respiratory tract infections in each season and determine their peak pre-and post-COVID-19-pandemic.

Study design
The present study was designed as a descriptive cross-sectional retrospective study.

Data collection
Data were collected from patient medical records through the electronic system. All nasopharyngeal swabs (NPS) were collected upon admission.  [1][2][3][4], Bordetella pertussis, Bordetella parapertussis, Chlamydia pneumoniae, and Mycoplasma pneumonia); then, these data that include the medical file number, date of admission, date of discharge, age upon admission, diagnosis upon admission, diagnosis upon discharge, length of stay, Pediatric Intensive Care Unit (PICU) admission, PICU length of stay, type of respiratory support and oxygen concentration, need for chest tube, nasopharyngeal swabs results, chest x-ray findings, investigations results including for CBC, CRP, procalcitonin, and cultures, need for steroid, need for antibiotics, and readmission within seven days were entered in REDCap system, cleaned up, and then exported to an Excel sheet.

Statistical analysis
Data were analyzed using JMP version 14. Descriptive data were presented as mean ± standard deviation for the continuous variables. Categorical variables were reported as frequency (percentage). Chi-square analyses were used to test the association between the COVID-19 pandemic and the seasonal variations of different viruses causing respiratory diseases in children.

Discussion
The present paper shows that most of the viruses causing respiratory illnesses in children decrease post-COVID-19 compared with the pre-COVID-19 period. However, the HRE virus showed the opposite, and a mild increase in HMPV is seen. Meanwhile, ADV showed almost no change, which could be related to the non-pharmacological intervention (NPI) (use of masks, social distancing, closure of workplaces and schools, hand hygiene, etc.).
Previous studies have reported that viral interference among influenza viruses, rhinovirus, and other respiratory viruses can affect viral infections at the host and population levels. In this study, rhinovirus infection considerably increased in children despite the recommended precautions. Since rhinovirus is a non-enveloped virus, it is relatively resistant to ethanol-containing disinfectants [3], and it can survive on environmental surfaces for a prolonged period of time [4]. This paper shows COVID-19's effect on the peak incidence of RSV, influenza A, HRE, and PIV. RSV showed no peak post-COVID-19, while its peak pre-COVID-19 was in winter. HRE's peak changed to autumn instead of winter during the pre-COVID-19 period. IA was noted in winter; however, post-COVID-19, it had two peaks in summer and autumn, while PIV's peak was in winter and in summer post-COVID-19. The United States Centers for Disease Control and Prevention (CDC) has also reported an increase in RSV activity in May to June 2021 [7], which is unusual for this period.
In contrast, in Australia, the percent of influenza tests that were positive continued to be very low (<0.01%), indicating limited influenza transmission in the community. Since early March 2020, this percentage has remained far lower than the usual range for the time of year [9]. Similarly, the US reported in May 2020 that the influenza hospital rates were 90% lower than during the low severity 2011/12 season with persistently low rates across the autumn/winter of 2020/21 [10].
Although the World Health Organization (WHO) and European Centre for Disease Prevention and Control (ECDC) have reported that influenza activity during the 2020/2021 influenza season did not increase above baseline with no indication of an autumn/winter spike, despite widespread and regular testing for influenza viruses, this has continued into the spring and summer of 2021, where influenza activity remained at interseasonal levels [10].
This paper has limitations include samples were from one center; however, we tried to expand our sample size by include all cases with positive NPA PCR Pre and Post COVID-19. Our study has some limitation which is small sample sizes at post-COVID-19 period and it was done in one center, we tried to partially compensate this issue, by including the whole years since our center start to work, and by doing the analysis for each period separately, then comparing virus' percentage not numbers.